A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

Qiong Fu, Ping Feng, Ling-Yun Sun, Xiao-Xia Zuo, Dong-Bao Zhao, Dong-Yi He, Hua-Xiang Wu, Wei Zhang, Wei Zhang, Fang Du, Chun-De Bao, Qiong Fu, Ping Feng, Ling-Yun Sun, Xiao-Xia Zuo, Dong-Bao Zhao, Dong-Yi He, Hua-Xiang Wu, Wei Zhang, Wei Zhang, Fang Du, Chun-De Bao

Abstract

Background: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA.

Methods: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48.

Results: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed.

Conclusions: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted.

Trial registration: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.

Conflict of interest statement

None.

Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

Figures

Figure 1
Figure 1
Flow chart showing the randomized distribution of the participants in the three groups: 99Tc-MDP combined with MTX, MTX, and 99Tc-MDP. 99Tc-MDP: 99Tc-methylene diphosphonate; MTX: Methotrexate.
Figure 2
Figure 2
ACR20/50/70 response rates and changes in DAS28[ESR] in the participants. (A) ACR20 at weeks 24 and 48. (B) ACR50 at weeks 24 and 48. (C) ACR70 at weeks 24 and 48. (D) Mean changes in DAS28[ESR] at week 48. ∗P < 0.05, MTX + 99Tc-MDP group vs.99Tc-MDP group; †P < 0.05, MTX + 99Tc-MDP group vs. MTX group; ‡P < 0.05, MTX group vs.99Tc-MDP group. 99Tc-MDP: 99Tc-methylene diphosphonate; ACR: American College of Rheumatology; ESR: Erythrocyte sedimentation rate; MTX: Methotrexate.
Figure 3
Figure 3
Cumulative percentage of radiographic progression. The changes in mTSS score were obvious in the MTX + 99Tc-MDP group and 99Tc-MDP alone group compared with the MTX alone group. 99Tc-MDP: 99Tc-methylene diphosphonate; MTX: Methotrexate; mTSS: Modified total Sharp score.
Figure 4
Figure 4
Radiographic changes of RA for the three treatment strategies. (A) Radiographic non-progression. (B) Mean changes in mTSS. (C) The mean changes in the joint space narrowing score at 48 weeks. (D) The mean change in the mTSS score at 48 weeks. mTSS: Modified total Sharp score; RA: Rheumatoid arthritis.

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Source: PubMed

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